Bipolar depression is an illness of recurring mood swings from the low of depression to the high of mania. It is commonly misdiagnosed as unipolar depression (major depressive disorder), says Shefali Miller, MD, because the first symptoms often occur from a major depressive episode.

True bipolar disorder includes recurrent episodes of mood elevation (mania or hypomania) as well as depression. It is less common than major depressive disorder. Bipolar disorder affects as much as 4 percent of the general population, Dr. Miller said at a presentation to the Stanford Health Library. It is a serious illness that carries a risk of suicide 20 to 30 times higher than in the general population.

“It’s really important to get help,” said Dr. Miller, an assistant clinical professor of psychiatry and behavioral sciences. Family and caregivers of the people who are ill need support as well. “This illness affects everyone,” Dr. Miller said.

The mood swings in bipolar illness are severe. A diagnosis of bipolar depression can be considered when a person experiences an episode of major depression that lasts at least two consecutive weeks, Dr. Miller said. Symptoms include a change in appetite or sleep, agitation or sluggishness and fatigue, feelings of low self-esteem and guilt, loss of interest or enjoyment in life, and thoughts of suicide.

The illness also includes episodes of mania that last at least one week, or episodes of a less severe state called hypomania that last for four days. Symptoms include a euphoric or irritable mood with increased energy, inflated self-esteem and grandiosity, less need for sleep, tendency to be more talkative, distractibility, risk-taking, and impulsivity. During a manic phase, people can be more active, agitated, and have racing thoughts or a rapid flight of ideas like “suddenly wanting to write a novel,” Dr. Miller said.

True mania is severe enough to require hospitalization, involve psychosis, or cause major problems like bankruptcy, divorce or imprisonment.

Bipolar illness is categorized into two main types. The first is bipolar I disorder, with recurring wide fluctuations in mood from mania to depression. The second is bipolar II disorder, having episodes of hypomania alternating with more dominant episodes of depression, Dr. Miller said. About half of people with bipolar illness have an episode of major depression first, before any mania episodes, so many are misdiagnosed as having depression alone. For either type, the episodes of depression tend to be the bigger burden that causes more disability in people’s lives than does mania or hypomania.

Studies have found that bipolar disorder overall is linked more closely to genetics than to environmental factors. A person who has a first-degree relative (in the immediate family) with bipolar illness faces a risk more than 10 times higher than others of also developing the disorder. Stated a different way, Dr. Miller said, 85 percent of the risk of developing bipolar disorder appears to be attributable to genetic (rather than environmental) factors.

That’s a much stronger genetic influence than what is seen in depression alone, Dr. Miller said. For depression, about 30 to 40 percent of risk is linked to heredity rather than environment.

Because bipolar disorder can be such a severe condition, the annual rate of suicide attempts is high: 3.9 percent compared with 0.5 percent in the general population, Dr. Miller said. The annual rate of suicide death is also high: 1.4 percent for bipolar people compared with 0.02 percent in the population. Suicide acts are far more likely to occur when depressed or mixed than during a pure manic state.

The burden of the illness extends to caregivers, who experience higher risk for depression, health problems and chronic medical conditions, Dr. Miller said.

There are a number of drugs used to treat bipolar illness that treat the acute phase, or onset, of depression or mania. There are also drugs approved for use after the acute phase, when people move to a period of remission. But the drugs don’t help everyone, especially long term.

“There is an unmet need for an effective and well-tolerated treatment for bipolar depression,” Dr. Miller said.

Overall, treatment options for bipolar disorder have increased since 1970, when doctors started using lithium, a mood stabilizer that has side effects including tremors. After 2000, a number of antipsychotic drugs were approved by the FDA for treating bipolar illness, such as risperidone, olanzapine, and quetiapine. But these antipsychotics carried a relatively high risk (more than 10 percent) of substantial side effects including weight gain and other metabolic changes.

Later antipsychotics that had somewhat lower risks of side effects were aripiprazole, ziprasidone, asenapine and most recently, lurasidone. Doctors also often prescribe antidepressants, which overall have lower risks of serious side effects. In general, however, the drugs that are most effective against bipolar disorder also have the most side effects, Dr. Miller said.

“We’re always doing this balancing act,” she said. “A lot of the medications we use have really bad side effects. That’s one of the challenges of treating this illness.”

In the past there has been a lot of concern that prescribing antidepressants for bipolar disorder will trigger a manic episode, Dr. Miller said. In recent years, a number of studies have found antidepressants just don’t work for this illness. “The main problem is they’re not effective,” she said. Still, she added, “we use them a lot.” That’s because they may help a few people, and they have fewer side effects and are cheap.

Only three drugs are approved by the FDA for treating bipolar depression: olanzapine/fluoxetine (a combination), quetiapine, and lurasidone. While they can help, each comes with a chance of side effects. Olanzapine/fluoxetine increases the risk of weight gain, insulin resistance, diabetes, sedation and elevated blood lipids. Quetiapine raises the risk for weight gain and sedation. Lurasidone may cause nausea or agitation and restlessness.

Drug treatment can be more effective when combined with psychotherapy for bipolar disorder, Dr. Miller said. Psychotherapy alone isn’t effective, but it can be combined with drug treatment to improve response. Evidence suggests psychotherapy is more effective for preventing bipolar relapse than for treatment of acute bipolar depression.

For people who aren’t helped much by drug treatment and psychotherapy, there are still other options. Because they have major drawbacks, these treatments are usually reserved for severe illness. One option, electroconvulsive therapy (ECT), can help ease severe depression. “It can work when everything else has not worked,” Dr. Miller said. But it also carries the risk of memory loss.

Another option is called repetitive transcranial magnetic stimulation, which is a stimulation of the scalp that is less invasive than ECT. So far, there are limited data on the effectiveness of this treatment for bipolar disorder, Dr. Miller said.

Another method that is still experimental uses ketamine, an anesthetic compound, for a rapid antidepressant effect. The drug is infused and its effect lasts only a few days. “It’s not clear if it’s sustainable,” Dr. Miller said. “It’s too new to know yet.”

Although bipolar disorder can be a debilitating condition, it may have a silver lining for some people, Dr. Miller said. It has been linked to creativity, particularly in artists like Vincent Van Gogh and the novelist Virginia Woolf. A study looked at more than 1,000 people who were subjects of biographies reviewed in the New York Times Book Review and found bipolar disorder was much more common in eminent poets, fiction writers and artists than in sports or military figures. While not diminishing the pain of the illness, Dr. Miller called the link “something to feel good about.”

At Stanford, Dr. Miller is conducting studies of two drug treatments for bipolar depression:

Suvorexant, a drug for insomnia related to bipolar disorder. To be eligible, people must be age 18 or older, diagnosed with bipolar disorder and currently experiencing insomnia. For more information, call (650) 498-8459.

Infliximab, a drug for people currently experiencing symptoms of depression who are diagnosed with bipolar disorder. Eligible people must be age 18 to 65. For more information, call (650) 723-9392.

About the Speaker
Shefali Miller, MD, received her medical degree from Columbia University and completed her medical residency at Stanford University Medical Center, where she works now in the bipolar disorders clinic. She is board-certified in psychiatry by the American Board of Psychiatry and Neurology.